The 1918 flu may have killed as many as 25 million in its first 25
weeks; in contrast, AIDS killed 25 million in its first 25 years.
The 1918 flu killed more people than the Great
War, known today as World War I (WWI).
It has been cited as the most devastating epidemic in
recorded world history. More people died of influenza in a single year
than in the four years of the Black Death Bubonic Plague from 1347 to
1351. The U.S. government has decided to post the recipe for
its eight gene segments
here.

Overview

Ray Kurzweil says “We have an existential threat now in the form of the
possibility of a bioengineered malevolent biological virus. With all the
talk of bioterrorism, the possibility of a bioengineered bioterrorism
agent gets little and inadequate attention. The tools and knowledge to
create a bioengineered pathogen are more widespread than the tools and
knowledge to create an atomic weapon, yet it could be far more
destructive. I’m on the
Army Science Advisory Group (a board of five
people who advise the Army on science and technology), and the Army is
the institution responsible for the nation’s bioterrorism protection.
Without revealing anything confidential, I can say that there is acute
awareness of these dangers, but there is neither the funding nor
national priority to address them in an adequate way.”

Ebola is the common term for a group of viruses belonging to genus
Ebolavirus, family Filoviridae, which cause Ebola
hemorrhagic fever.
The disease can be deadly and encompasses a range of symptoms, usually
including vomiting, diarrhea, general body pain, internal and external
bleeding, and fever. Mortality rates are generally high, ranging
from 50% to 90%, with the cause of death usually due to shock or
multiple organ failure.

Today more than a quarter of all deaths worldwide  15 million each
year
 are
due to infectious diseases. These include 4 million from respiratory
infections, 3 million from HIV/AIDS, and 2 million from waterborne
diseases such as cholera. This is a continuing and intolerable holocaust
that, while sparing no class, strikes hardest at the weak, the
impoverished, and the young.

The new realities of terrorism and suicide bombers pull us one step
further. How would we react to the devastation caused by a virus or
bacterium or other pathogen unleashed not by the forces of nature, but
intentionally by man?

No intelligence agency, no matter how astute, and no military, no matter
how powerful and dedicated, can assure that a small terrorist group
using readily available equipment in a small and apparently innocuous
setting cannot mount a first-order biological attack. With the rapid
advancements in technology, we are rapidly moving from having to worry
about state-based biological programs to smaller terrorist-based
biological programs.

It’s possible today to synthesize virulent pathogens from scratch, or
to engineer and manufacture
prions that, introduced undetectably over
time into a nation’s food supply, would after a long delay afflict
millions with a terrible and often fatal disease. It’s a new
world.

Though not as initially dramatic as a nuclear blast, biological warfare
is potentially far more destructive than the kind of nuclear attack
feasible at the operational level of the terrorist. And biological war
is itself distressingly easy to wage.

Regulations

Rules and regulations can slow down development of any bioweapons until
the BioShield is complete. We suggest that:

1) All commercial DNA synthesis houses have screening procedures. While
most DNA synthesis companies screen orders for dangerous sequences, a few
do not. This gives both the synthetic biologist community members and
outsiders access to feedstocks for both wild-type and
genetically-engineered bioweapons.

2) The government should create and endorse new watch-lists to improve
industry screening. Watch-lists are used to check DNA synthesis
orders for possible bioweapon sequences and are currently not
standardized by any single
agency, corporate or governmental. Current lists focus almost
exclusively on select agents and toxins. Many other potentially
dangerous sequences are not included. Current organism-level lists
generate a large number of false positives which must be examined by
hand. This makes screening impractical for oligo houses that fill up to
one thousand orders per day. The number of false positives will also
become a problem for DNA synthesis companies as their businesses
grow.

Better software and more specific sequence lists can potentially fix
these defects. Such tools would (a) make existing DNA synthesis
screening more accurate and sustainable, and (b) allow oligo companies
to start their own screening programs.

3) The government should create a confidential hotline for biosafety and
biosecurity issues. All experimenters contemplating “experiments of
concern” should obtain independent expert advice before proceeding. The
hotline should make such advice freely available to all experimenters,
including non-members (e.g. hackers) who cannot otherwise obtain such
advice from formal university, company, or NIH safety
committees. This would either be a parallel mechanism to the
system on the ground of
Institutional Review Boards
(IRBs) that handle this work in academia or the current mechanism should
be expanded to handle all experimenters.

The hotline should also encourage researches to investigate and, if
necessary, report dangerous behavior. The encouragement should be in
the form of rewards for finding any dangerous behavior.

Codes of Conduct

More generally, we think that the idea of codes of conduct for
biosecurity is somewhat misleading. Codes of conduct probably make
sense for biosafety, because in that case each biologist needs to be
continuously thinking about whether his or her experiment is being done
safely.

Biosecurity is different. The main thing we want to avoid here is
somebody doing an “experiment of concern” that makes weapons radically
easier or more effective. This is a one-time decision and most of the
knowledge needed to make that judgment does not really involve biology.
People have been building bioweapons for fifty years and if you aren’t
part of that community it’s very easy to guess wrong about whether your
experiment is harmless.

Some time ago, NIH funded a
grant to improve
our knowledge of how toxic botox really is. Sounds fine. But the
experimental method involved figuring out how to stabilize ultrapure
botox, which is something that the US and USSR both failed to do in the
sixties. Biologists can’t reliably know this kind of history or what’s
important, it’s not their subject and its not reasonable for every
biologist to learn it.

So we think that the room for codes of conduct is pretty limited. Our
suggestions would be:

Get a sanity check. If you think that you have an
experiment of concern, then get qualified outside advice.
Lifeboat Foundation Scientific Advisory Board member
Stephen M. Maurer is
working with people
at
Maryland, Duke, and Northwestern to set up a portal where people can
get
this advice. We think a public pronouncement that you should always
get
a qualified outside opinion is important and would stop the practice of
doing the experiment and then announcing it to the AP.

Make the community more transparent. If you look at how US
intelligence went about deciding whether the Nazis had a bomb project,
they used the worldwide physics community to find out who had suddenly
stopped teaching or dropped out of sight. So if we can make science
communities more transparent, then that’s presumably going to pay
dividends later on. You can imagine taking steps like holding
reunions, even a community web site with names would be
good.

A
related point is that there needs to be an understanding of when
telling the cops is right and moral  we have a post-McCarthy
confusion in this country. If the guy down the hall seems to be doing
something strange, I would say you have an ethical obligation to find
out. And, more than that, call in the University and ultimately the
FBI if you can’t satisfy yourself that nothing bad is going on. We
think a public pronouncement that yes, whistle-blowing is commendable
would immediately make terrorist projects riskier. This might not be a
huge barrier all by itself, but terrorists usually get tripped up on
relatively small things. And after the fact, it almost always turns
out that people had some inkling what the guy down the hall is doing.
So we think it would be worth doing.

First Level Barrier

We call for the development of a “first level barrier” by 1) Stockpiling
industrial disposable particulate respirators such as the N95, N99,
or
N10 types. This mask will
prevent the user from being infected, or if already infected, from
spreading it to other people. If a plague became serious, it would
probably be best for the government to put on TV spots that tell people
that your best chance of surviving a plague (natural or otherwise) is to
simply stay home. Which, by the way, is also the best way to stop
transmission.
2) Installation of intense UV field
generators in the HVAC system of aircraft and other public places as
described in our
report for Virgin Atlantic. 3) Stockpiling of antiviral drugs such as
Tamiflu and antibiotics such as
Cipro.

Technologies to Combat Biological Viruses

One technology to develop is
RNAi-based viral suppression. Also, further strategies for battling
viral infections are being developed by biotech and pharma companies,
such as research programs focusing on the use of decoy
oligonucleotides, aptamers, and other
small
molecules such as peptides and glycopeptides to inhibit viral fusion
with human cell membranes or function. These technologies are new and
largely unproven so the important and definitive times are ahead.

2) Development of “smart” materials such as
antiviral surface
coatings that are being tested for use in face masks and other
applications.

3) Further advances in sequencing technologies, ultimately reaching a
target of full virus sequencing within hours. As mentioned,
identification of the virus used for the development of a vaccine or
other treatment for an unknown virus necessitates the rapid sequencing
of its entire DNA or RNA genome. Sequencing technology is in widespread
use and is constantly decreasing in cost per segment sequenced as well as
in the time taken for the sequencing.

The relevant
outcomes of
development in this field will reduce sample preparation time as well as
expand the diversity of materials useful for isolation of viruses to
be sequenced (blood, saliva, skin, mucosa). As faster
sequencing
times and better sequence assembly software are constantly being
developed the need for these measures to be specifically undertaken is
of lesser importance. Examples for emerging rapid sequencing
technologies include
nanopore-based sequencing,
sequencing based on
nano-scale electronic and photonic effects, and sequencing performed
using
microarray-based fluorescently-tagged polymerase and
nucleotides.

4) Software-based treatment design. A longer term and expensive
(though
ultimately valuable) avenue of research, which would be useful in a
variety of medicinal applications, would be the development of a
comprehensive software system able to analyze the genetic makeup of a
virus as well as the proteins it expresses (its
proteome), which could
provide specific
epitopic
or
conformational targets to interfere with
the production, processing and function of these
molecules.

The initial
identification of viruses susceptibilities would help determine the most
likely effective antiviral treatments based on DNA, RNA, or
protein-based interference strategies. Software-based strategies should
also allow the identification of the optimal protein sequences to be
used as a vaccine, and be able to accelerate the “good guys” response in
the “arms race” as further bioengineered, malicious pathogens are
developed.

5) We need to develop a universal flu vaccine
which would protect against all or most strains of influenza.
We support Bill Gates’ $12 million
Universal Influenza Vaccine Development
Grand Challenge in partnership
with the family of Google Inc. co-founder Larry Page to accelerate the
development of a universal flu vaccine.

Engineered Bacteria and Prions

Infectious human viruses are almost always either airborne or spread by
direct person to person contact. The first mode of propagation of
deadly rapidly infective agents would be potentially suicidal in the
global sense for a terrorist group or nation. Such infections know no
boundaries imposed by nations or ideologies. (It would be possible for a
nation or terrorist group with sufficient resources to produce a vaccine
that would protect them against such a release… A scary scenario was
played out in fiction a few years ago in
Rainbow Six by Tom Clancy.)
The second mode would be far too slow in any event and good public
health counter-measures already exist for slowly propagating infectious
agents.

Because it would be suicidal for a terrorist group or nation to use
airborne infectious viruses, they may decide to use engineered bacteria
or prions instead. (Although suicidal terrorists do exist!) To combat
these threats, we propose frequent testing of the water supply, not just
for known bacteria but for the biologically necessary
consensus DNA
sequences that would be present even in engineered organisms. All
known
toxin-producing sequences should be tested for as well.

We also propose
more extensive testing of the meat supply for prion sequences and we are
definitely against the current government regulations which
prohibit
meat processors from doing extra prion tests at their own
expense! This testing would be expensive but we are
currently doing way too little of it. Additionally, testing air in
cities would be useful.

Note that technologies like
PCR get cheaper every day and large scale
testing of this kind would further reduce the per test
cost.

We support development of the
prion blood test being developed by Claudio A. Soto’s group. This
new test is a million times more sensitive than conventional
antibody-based techniques for detecting prions.

Conclusion

It would be more cost effective if those funding the BioShield set
specific goals and gave prize money to the people/organizations that
accomplished them than simply funding research without such
goals.

We propose that we take the measure of this threat and make preparations
today to engage it with the force and knowledge adequate to throw it
back wherever and however it may strike. It is time to accelerate the
development of antiviral and antibacterial
technology for the human population. The way
to combat this serious and ever-growing threat is to develop broad tools
to destroy viruses and bacteria. We have tools such as those based on
RNA
interference that can block gene expression. We can now sequence the
genes of a new virus in a matter of days, so our goal is within
reach!

We call for the creation of new technologies and the enhancement of
existing technologies to increase our abilities to detect, identify, and
model any emerging or newly identified infective agent, present or
future, natural or otherwise  we need to accelerate the expansion
of our capacity to engineer vaccines for immunization, and explore the
feasibility of other medicinals to cure or circumvent infections, and to
manufacture, distribute, and administer what we need in a timely and
effective manner that protects us all from the threat of bioengineered
malevolent viruses and microbial organisms. Time is running
out.

New York University’s
PLAN C (Planning with Large Agent-Networks against
Catastrophes):
Planning responses to Catastrophes using a novel agent-based model
simulation computational tool.
PLAN C was designed and developed by the NYU Bioinformatics Group under
the supervision of
Bud Mishra and with
the interdisciplinary
collaboration of a team of experts from the NYU Centre for Catastrophe
Preparedness and Response (CCPR).

Videos

The animation shows a number of molecular machines  ribosomes,
motors,
and more  working to move molecules and structures around a cell,
and
even to create the structures. It also shows a lot of membrane events,
and molecules working with and through membranes, and a few organelles.
It shows the molecules in their real molecular structure  these
are
renderings of experimental data, not artists’
conceptions.